rs886041715
Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PM1PM2PM5PP2PP3_StrongPP5_Moderate
The NM_020988.3(GNAO1):c.118G>A(p.Gly40Arg) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 15/23 in silico tools predict a damaging outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G40A) has been classified as Pathogenic.
Frequency
Consequence
NM_020988.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GNAO1 | NM_020988.3 | c.118G>A | p.Gly40Arg | missense_variant, splice_region_variant | 1/9 | ENST00000262493.12 | |
GNAO1 | NM_138736.3 | c.118G>A | p.Gly40Arg | missense_variant, splice_region_variant | 1/8 | ||
GNAO1 | XR_007064866.1 | n.865G>A | splice_region_variant, non_coding_transcript_exon_variant | 1/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GNAO1 | ENST00000262493.12 | c.118G>A | p.Gly40Arg | missense_variant, splice_region_variant | 1/9 | 1 | NM_020988.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.16e-7 AC: 1AN: 1396334Hom.: 0 Cov.: 25 AF XY: 0.00000143 AC XY: 1AN XY: 698062
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 17 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Equipe Genetique des Anomalies du Developpement, Université de Bourgogne | Jan 01, 2015 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at